Green light for CAR-T ARI0002h developed by Hospital Clínic-IDIBAPS for multiple myeloma patients
- ARI0002h: the first CAR-T developed entirely in Europe for multiple myeloma
- Optimising treatment with CAR-T therapy
- What is CAR-T Therapy?
CAR-T ARI0002h, developed at Hospital Clínic Barcelona-IDIBAPS, has been approved by the Committee for the Evaluation of Medicinal Products for Human Use of the Spanish Agency for Medicines and Health Products (AEMPS) for approval as a non-industrially manufactured advanced therapy drug for patients with relapsed multiple myeloma.
This is the second advanced therapy developed by the Clínic Barcelona-IDIBAPS teams to be authorised by the AEMPS for use in patients with haematological diseases.
The development of CAR-T at Clínic-IDIBAPS has the fundamental support of the ‘la Caixa’ Foundation and the Carlos III Institute of Health (ISCIII). It has also received funding from the Spanish Association Against Cancer (AECC) and the Bosch Aymerich Foundation.
Today at a press conference it was explained by the Minister of Health of the Generalitat de Catalunya, Dr. Manel Balcells; Dr. Josep M. Campistol, General Director of the Clínic Barcelona; Dr. Elías Campo, Director of IDIBAPS; Mr. Ignasi López, Director of the Area of Relations with Research and Health Institutions of the ‘la Caixa’ Foundation; Dr. Carlos Fernández de Larrea, haematologist at the Clínic and head of the Myeloma, amyloidosis, macroglobulinemia and other gammopathies group at IDIBAPS; Dr. Álvaro Urbano, coordinator of the CAR-T Programme at the Clínic-IDIBAPS and head of the Haemopoietic Progenitor Transplantation group at IDIBAPS; and Dr. Manel Juan, head of the Immunology Service at the Clínic and of the Immunogenetics and immunotherapy in autoinflammatory and immune response group at IDIBAPS.
The Catalan Minister of Health, Manel Balcells, said that "what we are doing here today is exceptional, the result of teamwork, of many talented people, and that it joins other initiatives that also coexist in Catalonia and that the sum means that we can be a benchmark for improving the quality of life of people suffering from different diseases such as leukaemia, lymphoma, myeloma and haematological diseases". And he added: "we are talking about the future, a future that is already present, and how to make this reach everyone, how we socialise these therapies".
In this sense, Balcells highlighted that in Catalonia "we have followed a country strategy around the creation of the Catalan centre for advanced therapies, which is underway, has been approved by the Government, has its budget and before the end of this month will have the first meeting of its steering committee".
Dr. Josep M. Campistol explained that, "getting the approval of the AEMPS Committee is a milestone and is the result of the efforts of many professionals and researchers at the hospital. This is the second CAR-T therapy developed at the hospital with the aim of offering the best therapeutic alternative for each patient and to carry it out we have had the support of the ARI project and the various entities and institutions that have supported us financially".
Dr. Elias Campo pointed out that, "CAR-T therapy is a paradigmatic example of how biomedical research of excellence improves the quality of life of people, in this case of CAR-T ARI0002h, of patients with multiple myeloma".
Mr. Ignasi López pointed out that, "the progress towards the approval of this treatment demonstrates the translational nature of immunotherapy research at Hospital Clínic. It is research aimed at improving people's health and quality of life. This is also one of our founding objectives. Reaching patients with solutions justifies all our efforts".
The approval of the AEMPS Committee is the step prior to the notification of the approval of the hospital exemption that Hospital Clínic Barcelona will receive in the coming days. The approval process from the hospital has been coordinated by the Clinical Pharmacology Service team, led by Dr. Gonzalo Calvo.
On the other hand, the Clínica de la Universidad de Navarra will be authorised as a second production centre, as it has also produced the CAR-T therapy for clinical trials.
ARI0002h: the first CAR-T developed entirely in Europe for multiple myeloma
Multiple myeloma is a type of cancer that affects plasma cells in the bone marrow. It accounts for 10% of blood cancers and, although several treatments are available, many patients develop resistance, leading to relapses and an urgent need for new therapies to treat them. This is where CAR-T therapies can play a key role.
CAR-T ARI0002h has been developed entirely at IDIBAPS by Dr. Álvaro Urbano-Ispizua's research group. It is the first European CART to demonstrate clinical efficacy in patients with multiple myeloma. Specifically, it is a CART that targets the BCMA antigen, which is found on the surface of myeloma tumour cells. Two previous studies led by the Clínic-IDIBAPS and published in the journals Lancet Oncology and Clinical Cancer Research have shown the efficacy of CAR-T ARI0002h in patients with multiple myeloma who have relapsed after at least two lines of treatment and are already exposed to the main drugs used in this disease.
The two studies validated the efficacy of the treatment in a total of 60 patients and the results showed that 95% of patients responded to treatment with a favourable toxicity profile.
Dr. Carlos Fernández de Larrea has led the clinical development of CART ARI0002h, in which seven Spanish hospitals have participated: Hospital Clínic in Barcelona, Clínica Universidad de Navarra, Hospital Universitario de Salamanca, Hospital Virgen de la Arrixaca in Murcia, Hospital 12 de Octubre in Madrid, Hospital Virgen del Rocío in Seville and Hospital Clínico Universitario de Santiago. The preparation of CARTs for administration to patients has been carried out at the Hospital Clínic de Barcelona, by the Immunology Service team led by Dr. Manel Juan, and at the Clínica Universidad de Navarra.
Optimising treatment with CAR-T therapy
The efficacy of the treatment is assessed not only by the patient's initial response, but also by the durability of this response. Thus, the researchers have also described the optimal way to administer the treatment and have identified biomarkers of response, which could improve patient selection and treatment personalisation.
The first dose is administered fractionally, in three aliquots, and 100 days after the first infusion, a booster dose is administered to provide a sustained response with low toxicity. This reduces the severity of adverse effects without reducing the efficacy of the treatment.
On the other hand, different factors and biomarkers have been analysed to predict the response and duration of response after treatment with ARI0002h. "Knowing which patients will respond favourably to the therapy will allow us to optimise the results, adjust the therapeutic strategy and minimise side effects," says Carlos Fernández de Larrea.
What is CAR-T Therapy?
CAR-T therapy (Chimeric Antigen Receptor T-Cell) is a treatment that involves genetically modifying the patient's T-cells so that they can recognise and attack cancer cells.